In this project, Parabon NanoLabs will employ its Essemblix(tm) Drug Development Platform, a combination of computer-aided design (CAD) software and DNA nano-fabrication technology, to produce artificial vaccines against the biothreat agent ricin on DNA origami decorated first with natural epitopes and ultimately with artificial epitotopes (hereafter"mimotope") constructed from a predefined set of"building block molecules."Although this project focuses on a single biothreat agent, the ultimate goal is to advance the Essemblix technology such that, given an epitope for a potential biothreat agent, Essemblix will allow the production of mimotopes that can mimic the original epitope sufficiently to bind target antibodies with high affinity. In Phase I, we demonstrated Essemblix enables building block molecules to be arranged on origami in complex presentation patterns of the variety known to elicit rapid and potent immune response via T cell-independent activation and these techniques will be applied in Phase II. The resultant artificial vaccines, produced with natural and artificial epitopes, will be evaluated in murine studies to test their immunogenecity and toxicity, and a lead compound will be selected for further study, culminating in a demonstration of potency with lethal ricin challenge in mouse.